PROJECT SUMMARY Chronic pain in childhood is a significant public health concern with median prevalence rates of 11 to 38%, with 3 to 5% of children suffering from significant pain-related disability (~3.5 million children in the US). Notwithstanding the physical and psychological consequences on overall health, chronic pain in childhood results in high levels of healthcare utilization and can predispose the development of chronic pain in adulthood. Fear is a particularly salient influence on pain outcomes and is the focus of the current research proposal. A significant proportion of youth with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Beyond the individual, contextual influences substantially impact fear learning. Parents are profoundly affected when their child experiences pain and their (mal)adaptive response impacts outcomes. Thus, defining adolescent fear learning in chronic pain must incorporate parent distress and behavior. In the context of treatment, decreasing pain- related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. Although it is recognized that high levels of pain-related fear can be detrimental, the neurobiological mechanisms for acquisition and extinction of fear have yet to be defined in pain patients. This is particularly germane during adolescence where neuronal properties are primed for modification by experience and the peak onset of chronic pain in childhood occurs. Moreover, extinction, the primary means of eradicating fear, is not consistently effective as fear may return when in a new context or under stress. Thus, more robust techniques are needed to diminish fear in a context-independent fashion. One method to prevent the return of fear is disruption of fear memory reconsolidation, where extinction occurs in a time window during which the fear memory is labile. This method, established in rodents and humans, has yet to be demonstrated in pediatric pain patients. This proposal investigates the mechanisms underlying fear learning, fear extinction, and disruption of fear reconsolidation in adolescents with chronic pain and healthy controls using behavioral and neuroimaging measures with the long-term goal of improving exposure-based treatments for adolescents with chronic pain. Aim 1 examines acquisition and extinction of fear learning behaviorally and neurobiologically in adolescents with chronic pain and low or high pain-related fear and healthy controls with consideration of the influence of parent fear and avoidance behavior. Aim 2 examines enhancement of fear extinction with disruption of fear memory reconsolidation. Currently, the treatment of chronic pain is suboptimal. Significant breakthroughs require a mechanistic understanding of key processes underlying pain-related dysfunction. Defining behavioral and neurobiological mechanisms of fear learning and extinction will lead to advancements in our understanding and treatment of persistent pain in adolescents.